Asymptomatic monkeypox infection: a call for greater control of infection and transmission
Authors: Abdullah Reda, Amr Ehab El-Qushayri, Jaffer Shah
Journal: The Lancet Microbe (2022)

Effective public health response to the current monkeypox virus global health emergency requires quantification of asymptomatic infections. We collected evidence on the prevalence of asymptomatic infections through a literature search of five databases (Web of Science, Google Scholar, PubMed, Scopus, and Virtual Health Library) on Aug 30, 2022, with no restrictions on country of publication, using the following search terms: ("asymptomatic" OR "no symptom") AND ("monkeypox" OR "MPV" OR "MPX" OR "monkey pox" OR "monkeypox virus"). We included only studies that recruited patients from the current outbreak, which began in May, 2022. Both authors were involved in the screening process in addition to another phase of manual searches to avoid missing any relevant publications, including cohort, cross-sectional, case series, and case report studies. Of the 837 reports screened, we found two studies that assessed asymptomatic infection among cases of monkeypox virus infection: a study by De Baetselier and colleagues1De Baetselier I Van Dijck C Kenyon C et al.Retrospective detection of asymptomatic monkeypox virus infections among male sexual health clinic attendees in Belgium.Nat Med. 2022; (published online Aug 12.)https://doi.org/10.1038/s41591-022-02004-wCrossref PubMed Scopus (100) Google Scholar and another by Ferré and colleagues.2Ferré VM Bachelard A Zaidi M et al.Detection of monkeypox virus in anorectal swabs from asymptomatic men who have sex with men in a sexually transmitted infection screening program in Paris, France.Ann Intern Med. 2022; (published online Aug 16.)https://doi.org/10.7326/m22-2183Crossref PubMed Scopus (63) Google Scholar Across the two studies, among 807 participants who underwent PCR testing for monkeypox virus infection, 288 (36%) cases of monkeypox virus infection were detected (table). Among these cases, the prevalence of asymptomatic monkeypox virus infection was 6% (three [75%] of four participants in De Baetselier and colleagues' study1De Baetselier I Van Dijck C Kenyon C et al.Retrospective detection of asymptomatic monkeypox virus infections among male sexual health clinic attendees in Belgium.Nat Med. 2022; (published online Aug 12.)https://doi.org/10.1038/s41591-022-02004-wCrossref PubMed Scopus (100) Google Scholar and 13 [5%] of 284 participants in Ferré and colleagues' study).2Ferré VM Bachelard A Zaidi M et al.Detection of monkeypox virus in anorectal swabs from asymptomatic men who have sex with men in a sexually transmitted infection screening program in Paris, France.Ann Intern Med. 2022; (published online Aug 16.)https://doi.org/10.7326/m22-2183Crossref PubMed Scopus (63) Google ScholarTableCharacteristics of included studiesDe Baetselier et al (2022)1De Baetselier I Van Dijck C Kenyon C et al.Retrospective detection of asymptomatic monkeypox virus infections among male sexual health clinic attendees in Belgium.Nat Med. 2022; (published online Aug 12.)https://doi.org/10.1038/s41591-022-02004-wCrossref PubMed Scopus (100) Google ScholarFerré et al (2022)2Ferré VM Bachelard A Zaidi M et al.Detection of monkeypox virus in anorectal swabs from asymptomatic men who have sex with men in a sexually transmitted infection screening program in Paris, France.Ann Intern Med. 2022; (published online Aug 16.)https://doi.org/10.7326/m22-2183Crossref PubMed Scopus (63) Google ScholarCountryBelgiumFranceStudy populationMen undergoing anorectal or oropharyngeal sampling for gonorrhoea or chlamydia testing at a large sexual health clinic in BelgiumMen who have sex with men undergoing regular screening for gonorrhoea or chlamydia under programme for people receiving pre-exposure prophylaxis or antiretroviral treatment for HIVNumber of participants tested for monkeypox virus224583Diagnostic methodPCRPCRCases of monkeypox virus infection, n/N (%)4/224 (2%)284/583 (49%)Asymptomatic infections among cases of monkeypox virus infection, n/N (%)3/4 (75%)13/284 (5%)Characteristics of asymptomatic casesVaccinated against smallpox, n/N0/3..Orthopox-directed IgG antibody titres*Serum samples obtained between days 21 and 37 after initial PCR testing; lower limit of detection 1:20., range1:40–1:320..Sexual activity without condom in month before testing, n/N (%)3/3 (100%)..Sexual contact during foreign travel in 2 weeks before testing, n/N (%)2/3 (67%)..Monkeypox virus replication competence (by culture), n/N (%)2/3 (67%)..* Serum samples obtained between days 21 and 37 after initial PCR testing; lower limit of detection 1:20. Open table in a new tab The current evidence of asymptomatic monkeypox virus infections from our study supports the need for universal infection and transmission control efforts to curb increased transmission by undetected monkeypox virus carriers. This need has also been shown by Maruotti and colleagues' study,3Maruotti A Böhning D Rocchetti I Ciccozzi M Estimating the undetected infections in the monkeypox outbreak.J Med Virol. 2022; (published online Aug 27.)https://doi.org/10.1002/jmv.28099Crossref Scopus (8) Google Scholar which used a capture–recapture-based estimation of the true monkeypox cases and indicated that the true number of cases might be 3·16 times the number of announced cases. Maruotti and colleagues suggested that this underestimation of the actual number of cases might be due to undetected spread of monkeypox virus outside of the African continent, the historical origin of the disease. Furthermore, data from previous outbreaks4Guagliardo SAJ Monroe B Moundjoa C et al.Asymptomatic orthopoxvirus circulation in humans in the wake of a monkeypox outbreak among chimpanzees in Cameroon.Am J Trop Med Hyg. 2020; 102: 206-212Crossref PubMed Scopus (37) Google Scholar, 5Jezek Z Nakano JH Arita I Mutombo M Szczeniowski M Dunn C Serological survey for human monkeypox infections in a selected population in Zaire.J Trop Med Hyg. 1987; 90: 31-38PubMed Google Scholar have shown that monkeypox cases can be asymptomatic, although this evidence was based on a serological diagnosis with no molecular testing of the presence and replication-competence reported by De Baetselier and colleagues.1De Baetselier I Van Dijck C Kenyon C et al.Retrospective detection of asymptomatic monkeypox virus infections among male sexual health clinic attendees in Belgium.Nat Med. 2022; (published online Aug 12.)https://doi.org/10.1038/s41591-022-02004-wCrossref PubMed Scopus (100) Google Scholar According to previous studies, the role of asymptomatic transmission of orthopox viruses is negligible.6Fenner F A successful eradication campaign. Global eradication of smallpox.Rev Infect Dis. 1982; 4: 916-930Crossref PubMed Google Scholar, 7Sarkar JK Mitra AC Mukherjee MK De SK Mazumdar DG Virus excretion in smallpox. 1. Excretion in the throat, urine, and conjunctiva of patients.Bull World Health Organ. 1973; 48: 517-522PubMed Google Scholar Although the smallpox virus could be detected in the upper respiratory tract of asymptomatic contacts of smallpox cases, quarantine and contact tracing were the most effective measurements in eradicating the disease, together with vaccination. Similarly, containing previous monkeypox outbreaks was achievable by such measures in endemic areas.8Petersen E Kantele A Koopmans M et al.Human monkeypox: epidemiologic and clinical characteristics, diagnosis, and prevention.Infect Dis Clin North Am. 2019; 33: 1027-1043Summary Full Text Full Text PDF PubMed Scopus (265) Google Scholar However, these measures might not be adequate in controlling the current outbreak because sexual activity seems to be the main mechanism of transmission for monkeypox, and contact tracing might not be feasible in situations involving frequent sexual activities with anonymous partners. National surveillance programmes should be conducted, particularly among populations at high risk of infection, to detect asymptomatic cases. Such surveillance will require rapid diagnostic or home-based tests that could identify undiagnosed infections. Surveillance at a country's entry points (eg, airports) might be effective, particularly in non-endemic countries with little evidence of local transmission, similar to approaches previously suggested for asymptomatic COVID-19 transmission.9Ma Q Liu J Liu Q Kang L Liu R Jing W et al.Global percentage of asymptomatic SARS-CoV-2 infections among the tested population and individuals with confirmed COVID-19 diagnosis: a systematic review and meta-analysis.JAMA Netw Open. 2021; 4e2137257Crossref Scopus (180) Google Scholar, 10Al-Qahtani M AlAli S AbdulRahman A Salman Alsayyad A Otoom S Atkin SL The prevalence of asymptomatic and symptomatic COVID-19 in a cohort of quarantined subjects.Int J Infect Dis. 2021; 102: 285-288Summary Full Text Full Text PDF PubMed Scopus (30) Google Scholar Health-care providers should also establish a proper differential diagnosis before excluding monkeypox, especially considering the increasing non-specific presentations of the disease. Finally, cases could be decreased and the processes of case identification and contact tracing could be facilitated by individuals limiting their numbers of sexual partners and by limitations on areas and gatherings where people commonly engage in anonymous sexual activities. We declare no competing interests. Mpox screening in high-risk populations finds no asymptomatic casesIn their Correspondence, Abdullah Reda and colleagues emphasised the importance of undiagnosed mpox (formally known as monkeypox) cases and called for surveillance with rapid diagnostic or home-based tests.1 We agree that the threshold for testing or screening at-risk populations should be low at the beginning of an epidemic with a new pathogen, to ascertain the nature and prevalence of atypical presentations. Full-Text PDF Open Access